記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Previous cross-sectional studies have reported that adolescent patients with anorexia nervosa (AN) showed global gray matter volume (GMV) reductions at the acute phase which were restored at the weight-recovered phase, compared with healthy controls (HC). However, few studies have investigated white matter volume (WMV) or cortical thickness in the context of AN, and results have been inconsistent. Voxel-based morphometry analyses for GM and WM, and cortical thickness analyses for GM were conducted in 31 adolescent patients with AN (vs. 18 HC) in the acute phase, and 16 patients with AN (vs. 13 HC) in the follow-up weight-recovered phase, over an approximately 1-year follow-up interval. At the acute phase, the AN patients showed significant reductions of GMVs and cortical thickness in widespread brain regions, compared with HC. Significant WMV reductions were identified in the bilateral superior longitudinal fascicle, superior thalamic radiation, corona radiata, and fornix, pons, and medulla in the patients. At the weight-recovered phase, the AN patients showed a significant GMV reduction in the left hippocampus, and a WMV reduction in the pons, compared with the HC. There was no difference in cortical thickness between two groups at the weight-recovered phase. In conclusion, the widespread volumetric reductions in GM and WM, and reduced cortical thickness observed in AN patients in the acute phase were not evident in the follow-up weight-recovered phase. The volume reductions observed in the hippocampus and pons in the weight-recovered phase could potentially reflect delayed neurogenesis or recovery from starvation in the AN patients.

DOI： 10.1007/s11682-021-00622-5

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Suicide remains one of the leading causes of death among adolescents. Although recent studies have suggested a strong association between auditory hallucinations and suicidal behaviors, little is known regarding the association between suicidal behaviors and visual hallucinations, which are also common among adolescent psychiatric patients. METHOD: A cross-sectional study of all first-time patients aged 10-15 years was conducted at three child and adolescent psychiatric outpatient facilities in Kanagawa Prefecture, Japan, from April 2015 to March 2018. Self-reported questionnaires were administered to evaluate auditory and visual hallucinations, suicide planning, and suicide attempts within the two weeks prior to the first visit. Our logistic regression model included three covariates (sex, age, and presence of major depressive episode) for adjustments. Among the 1285 respondents, 37 who had moderate or severe intellectual disability were excluded, leaving 1248 for analysis. RESULTS: Among the 1069 patients who completed questionnaire items on hallucinations, 230 (21.5%) experienced auditory or visual hallucinations. After controlling for all confounders, visual hallucinations, but not auditory hallucinations, were significantly associated with increased odds of suicide planning (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.5-4.1). In contrast, auditory hallucinations, but not visual hallucinations, were significantly associated with increased odds of suicide attempts (OR 2.8, 95% CI 1.3-6.1). No interaction effects were observed between suicidal behaviors and auditory or visual hallucinations. CONCLUSIONS: Clinicians should consider the prevalence of both auditory and visual hallucinations among young adolescent patients, with emphasis on auditory hallucinations, given their association with suicide attempts.

DOI： 10.1111/camh.12504

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記述言語：日本語   出版者・発行元：(公社)日本小児科学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.neulet.2020.135588

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction: Hashimoto's thyroiditis, which is characterized by anti-thyroid antibodies such as the anti-thyroglobulin (Tg) antibody and anti-thyroid peroxidase (TPO) antibody, is one of the autoimmune diseases associated with psychiatric illnesses. We previously reported a high prevalence of antibodies to N-terminals of N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN1-NT and GluN2B-NT2) among psychiatric patients with anti-thyroid antibodies. However, it remains unclear whether the presence of anti-thyroid antibodies influences antibodies to GluN1-NT or GluN2B-NT2 among psychiatric patients. The present study aims to examine antibodies to GluN1-NT and GluN2B-NT2 in psychiatric patients with anti-thyroid antibodies (PPATs) and in those without (non-PPATs). Material and methods: We recruited psychiatric inpatients aged 20-60 years. Patients were excluded if they had a history of neurological diseases, dementia, developmental disorders, tumors, or autoimmune diseases except autoimmune thyroiditis. The rest of the participants were divided into two groups according to the presence of serum anti-Tg and anti-TPO antibodies. We investigated serum and cerebrospinal fluid (CSF) antibodies to GluN1-NT and GluN2B-NT2 using an enzyme-linked immunosorbent assay (ELISA). Results: We initially recruited seventy-three psychiatric inpatients. Forty-six patients were excluded because of the exclusion criteria. Eighteen PPATs and nine non-PPATs were ultimately enrolled. We also collected stored sera of eighteen healthy controls (HCs) who were age- and sex-matched with PPATs. The optical densities (ODs) of serum antibodies to GluN1-NT (p = 0.0020) and GluN2B-NT2 (p = 0.039) were significantly higher in PPATs than in HCs. The ODs of CSF antibodies to GluN1-NT (p = 0.030) and GluN2B-NT2 (p = 0.017) as well as the positive ratios of those antibodies were significantly higher in PPATs than in non-PPATs. Conclusion: Our finding indicates that detecting anti-thyroid antibodies in psychiatric patients would be a clue to consider psychiatric conditions related to antibodies to GluN1-NT/GluN2B-NT2. Further studies focusing on the relationship between PPATs and antibodies to GluN1-NT/GluN2B-NT2 are needed.

DOI： 10.1016/j.heliyon.2020.e05677

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記述言語：日本語   出版者・発行元：(一社)日本総合病院精神医学会  

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記述言語：英語   出版者・発行元：(一社)日本認知症学会  

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記述言語：英語   出版者・発行元：(一社)日本認知症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.schres.2020.08.028

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jns.2020.116829

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The present study investigated the effects of plasma matrix metalloproteinases (MMPs) on longitudinal changes in Alzheimer's disease (AD)-related biomarkers in cerebrospinal fluid (CSF), brain atrophy, and cognitive function in patients with mild cognitive impairment due to AD (MCI-AD). METHODS: We used data from the Alzheimer's Disease Neuroimaging Initiative database. We included 95 ApoE4-positive patients with MCI-AD who were confirmed to have low Aβ42 and/or high phosphorylated-tau (p-tau) in CSF. We obtained baseline demographic data, plasma MMP levels, including MMP-1, -2, -7, -9, -10, and tissue inhibitor of MMP-1 (TIMP-1), longitudinal annual data on Aβ42, total tau, and p-tau in CSF, MRI-measured hippocampal volumes, and cognitive function evaluated by the Mini-Mental State Examination (MMSE) and AD Assessment Scale-11 (ADAS-11) over 4 years. We examined the effects of baseline MMP levels on longitudinal changes in CSF AD biomarkers, hippocampal volumes, and cognitive function using a linear mixed regression analysis. RESULTS: No significant differences were observed in baseline plasma MMP levels between MCI-AD patients and control subjects, except for MMP-10, which was significantly lower in MCI-AD than in controls. The baseline levels of MMPs did not correlate with longitudinal changes in CSF biomarkers. Declines in hippocampal volumes and cognitive function evaluated by MMSE and ADAS-11 were significantly faster in MCI-AD patients with high-MMP-9 levels at baseline than in those with middle and low MMP-9 levels at baseline. CONCLUSION: High plasma MMP-9 levels in MCI-AD patients might enhance neurodegeneration and cognitive decline.

DOI： 10.1016/j.jns.2020.116989

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Use of the antipsychotic drug olanzapine by patients with schizophrenia is associated with autonomic nervous system (ANS) dysfunction. It is presumed that there are interindividual differences in ANS dysfunction that correspond to pharmacogenetics. In this study, we investigated whether genetic polymorphisms in ABCB1, CYP1A2, and UGT1A4 are associated with this observed ANS dysfunction. METHODS: A total of 91 schizophrenia patients treated with olanzapine monotherapy participated in this study. A power spectral analysis of heart rate variability was used to assess ANS activity. The TaqMan system was used to genotype seven single nucleotide polymorphisms (SNPs) in CYP1A2 (rs2069514 and rs762551), UGT1A4 (rs2011425), and ABCB1 (rs1045642, rs1128503, rs2032582, rs2235048). RESULTS: Sympathetic nervous activity was significantly higher in individuals with the UGT1A4 rs2011425 G allele than in those with the UGT1A4 rs2011425 non-G allele (sympathetic activity, p = .001). Furthermore, sympathetic nervous activity was also significantly associated with UGT1A4 rs2011425 genotype as revealed by multiple regression analysis (sympathetic activity, p = .008). CONCLUSIONS: We suggest that the UGT1A4 rs2011425 polymorphism affects olanzapine tolerability because it is associated with the observed side effects of olanzapine in schizophrenia patients, namely sympathetic dysfunction.

DOI： 10.1186/s12888-020-02492-5

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：(一社)日本認知症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: People with depression have autonomic function disturbances. In Japan, workers who take leave due to depression often undergo a work-focused intervention program called the return to work (RTW) program at a mental health hospital during their leave of absence. However, its biological efficacy remains unclear. We investigated the biological efficacy of the RTW program, including changes in autonomic nervous system (ANS) activity, in workers on sick leave due to depression in Japan. Methods: The study involved 104 workers on sick leave due to major depressive disorder or bipolar disorder who underwent the RTW program for 3 months in Yokohama City University Hospital. The ANS activity of all patients was evaluated using heart rate variability at the beginning and end of the 3-month RTW program. Psychiatric symptoms were evaluated using the Montgomery-Åsberg Depression Rating Scale-Japanese (MADRS-J) and Social Adaptation Self-evaluation Scale (SASS). We followed up 3 months after the end of the program and investigated the association between the success in returning to work within 3 months after the end of the RTW program and several factors, including ANS activity, depressive symptoms, and demographic factors. Results: Parasympathetic activity was significantly higher and depressive symptom severity was significantly lower at program end than at baseline. Logistic regression analysis showed that the change in depressive symptoms was significantly associated with success in returning to work. Conclusion: We suggest that the RTW program improves parasympathetic activity as well as psychiatric symptoms. ANS activity was not a predictor of a successful return to work within 3 months after the end of the program in workers on sick leave due to depression, but further studies with a larger sample size are needed.

DOI： 10.1016/j.heliyon.2019.e02151

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.heliyon.2019.e02151.

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Patients with schizophrenia have a higher mortality risk than the general population. Additionally, the autonomic nervous system (ANS) activity of patients with schizophrenia is lower and more dysfunctional than that of the general population. Nonetheless, the association between ANS dysfunction and mortality in schizophrenia is unclear. The aim of this study was to investigate the association between ANS activity and mortality in schizophrenia and to evaluate the predictive values of heart rate variability for long-term survival. METHODS: This study involves the 10-year follow-up of a sample population consisting of 59 Japanese inpatients with schizophrenia between 60 and 70 years of age from 2007 to 2016. The ANS activity of all patients was evaluated using heart rate variability in 2007. RESULTS: Fifty-three participants could be followed up because they stayed in the hospital during the follow-up period. Of these patients, 11 died during follow-up. Their mean age at death was 70.55 ± 3.45 years. The parasympathetic activity of nonsurvivors was significantly lower than that of survivors, and multiple logistic regression analysis showed a significant association between death and parasympathetic activity. CONCLUSION: We suggest that decreased parasympathetic activity could be associated with 10-year all-cause mortality in older schizophrenic patients.

DOI： 10.1016/j.comppsych.2018.08.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: There are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction. Accordingly, to clarify the interindividual differences in the adverse effects of specific atypical antipsychotics in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in patients with schizophrenia. METHODS: In total, 233 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 89 participants received risperidone, 69 olanzapine, 48 aripiprazole, and 27 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. Four single nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs1128503, rs2032582, and rs2235048) were genotyped using the TaqMan method. RESULTS: For aripiprazole, sympathetic and total autonomic nervous activities were significantly lower in the rs1045642 T allele carrier-rs2235048 C allele carrier group than in the rs1045642 non-T allele carrier-rs2235048 non-C allele carrier group. In addition, in the aripiprazole group, the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582) was associated with decreased ANS activity. However, there were no significant associations between ANS activity and ABCB1 gene polymorphisms in the risperidone, olanzapine, and quetiapine groups. Multiple regression analysis revealed that sympathetic and total nervous activities were significantly associated with the ABCB1 rs1045642-rs2235048 genotype and the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582). CONCLUSION: We suggest that ABCB1 genetic polymorphisms affect aripiprazole-related ANS dysfunction but do not affect risperidone-, olanzapine-, or quetiapine-related ANS dysfunction.

DOI： 10.1186/s12888-018-1817-5

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記述言語：英語  

DOI： 10.1016/j.schres.2017.11.020

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Antipsychotic drugs are associated with autonomic nervous system (ANS) dysfunction in patients with schizophrenia, but the effects of individual atypical antipsychotic drugs are not clear. This study investigated how four atypical antipsychotic drugs-risperidone, olanzapine, aripiprazole, and quetiapine-differ in their effects on ANS activity. A total of 241 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 90 participants received risperidone, 68 olanzapine, 52 aripiprazole, and 31 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. The quetiapine group showed significantly diminished sympathetic and parasympathetic activity compared with the risperidone and aripiprazole groups and significantly lower sympathetic activity relative to olanzapine. In addition, multiple regression analysis showed that the type of antipsychotic drug significantly influenced ANS activity. We suggest that, among the antipsychotics examined-risperidone, olanzapine, aripiprazole and quetiapine-quetiapine has the strongest effect on ANS activity.

DOI： 10.1016/j.schres.2017.07.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: Long-acting injections (LAIs) of antipsychotics show distinct pharmacokinetic profiles from oral antipsychotics (OAPs). Although there may be differences in adverse event frequency, any differences in their effects on autonomic nervous system (ANS) remain unclear. Patients and methods: In total, 270 schizophrenic patients were recruited in this study: 241 received OAPs (risperidone, olanzapine, quetiapine, or aripiprazole) and 29 received LAIs (risperidone LAI, aripiprazole LAI, or paliperidone palmitate) as monotherapy. Heart rate variability was measured as an index of ANS activity, and the low-frequency (0.03-0.15 Hz) component, high-frequency (0.15-0.40 Hz) component, and total power (0.03-0.40 Hz) were calculated. Components were compared between the groups using t-tests. Results: A significant difference was detected in the low-frequency component between the OAP and LAI groups (P=0.046). No significant difference was found in total power or the high-frequency component between the two groups. Conclusion: Compared with OAPs, LAIs have fewer adverse effects on ANS activity, particularly the low-frequency component, as determined using a spectral analysis of heart rate variability.

DOI： 10.2147/NDT.S173617

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記述言語：日本語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Patients with schizophrenia have abnormal autonomic nervous system (ANS) activity compared with the general population. One reason for this difference is the muscarinic affinity for antipsychotic drugs; therefore, single nucleotide polymorphisms (SNPs) of the muscarinic receptor gene influence this ANS dysfunction. This study sought to determine the effect of SNPs of the cholinergic muscarinic receptor (CHRM) gene on ANS activity in patients with schizophrenia receiving antipsychotic drugs. METHODS: A total of 173 Japanese patients with schizophrenia were included in this study. Heart rate variability (HRV) was measured as an index of ANS activity. SNPs in CHRM1 (rs542269 and rs2075748), CHRM2 (rs324640, rs8191992, rs1824024, and rs7810473), and CHRM3 (rs3738435, rs4620530, and rs6429157) were genotyped using the TaqMan® method. Patients were grouped according to standard equivalent conversions of chlorpromazine (CP) into a high-CP group (HG; ≥1,000 mg) and a low-CP group (LG; <1,000 mg). ANS activity was compared between the groups. In addition, we compared the total, low-frequency (LF), high-frequency (HF), and LF/HF components of the patients' HRV, and the genotype of the SNPs in both the HG and LG groups. Bonferroni correction was applied for multiple comparisons, and the Bonferroni-corrected critical p value was <0.005. RESULTS: The A allele of the CHRM2 rs8191992 polymorphism in HG was associated with decreased ANS activity. CONCLUSION: Our results show reduced ANS activity in association with the CHRM2 rs8191992 polymorphism in patients with schizophrenia on high-dose antipsychotics. CHRM2 polymorphisms may play an important role in ANS activity in patients with schizophrenia.

DOI： 10.1159/000452770

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記述言語：英語   出版者・発行元：日本生物学的精神医学会・日本神経精神薬理学会  

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